Cationic dextrin nanoparticles for effective intracellular delivery of cytochrome C in cancer therapy†

Abstract

Intracellular protein delivery shows promise as a selective and specific approach to cancer therapy. However, a major challenge is posed by delivering proteins into the target cells. Despite the development of nanoparticle (NP)-based approaches, a versatile and biocompatible delivery system that can deliver active therapeutic cargo into the cytosol while escaping endosome degradation remains elusive. In order to overcome these challenges, a polymeric nanocarrier was prepared using cationic dextrin (CD), a biocompatible and biodegradable polymer, to encapsulate and deliver cytochrome C (Cyt C), a therapeutic protein. The challenge of endosomal escape of the nanoparticles was addressed by co-delivering the synthesized NP construct with chloroquine, which enhances the endosomal escape of the therapeutic protein. No toxicity was observed for both CD NPs and chloroquine at the concentration tested in this study. Spectroscopic investigations confirmed that the delivered protein, Cyt C, was structurally and functionally active. Additionally, the delivered Cyt C was able to induce apoptosis by causing depolarization of the mitochondrial membrane in HeLa cells, as evidenced by flow cytometry and microscopic observations. Our findings demonstrate that an engineered delivery system using CD NPs is a promising platform in nanomedicine for protein delivery applications.